Malaria in humait a county, state of Amazonas, Brazil. XIX - evaluation of clindamycin for the treatment of patients with Plasmodium falciparum infection

A total of 207 patients with malaria caused by Plasmodium falciparum were submitted to 5 different treatment schedules with clindamycin from 1981 to 1984: A - 89 patients were treated intravenously and orally, or intramuscularly and orally with 20 mg/kg/day divided into two daily applications for 5 to 7 days; B-40 patients were treated orally with 20 mg/kg/day divided into two daily doses for 5 to 7 days; C-27 patients were treated with 20 mg/kg/day intravenously or orally divided into two daily applications for 3 days; D-16 patients were treated orally and/or intravenously with a single daily dose of 20 to 40 mg/kg/day for 5 to 7 days; E-35 patients were treated orally with 5 mg/kg/day divided into two doses for 5 days. Patients were examined daily during treatment and reexamined on the 7th, 24th, 21st, 28th and 35th day both clinically and parasitologically (blood test). Eighty three (40.1%) had moderate or severe malaria, and 97 (46.8%) had shown resistance to chloroquine or to the combination ofsulfadoxin and pyrimethamine. The proportion of cured patients was higher than 95% among patients submitted to schedules A and B. Side effects were only occasional and of low intensity. Three deaths occurred (1.4%), two of them involving patients whose signs and symptoms were already very severe when treatment was started. Thus, clindamycin proved to be very useful in the treatment of patients with malaria caused by Plasmodium falciparum and we recommend schedule A for moderate and severe cases and Bfor initial cases.

Usefulness of serology for the evaluation of Trypanosoma cruzi transmission in endemic areas of Chagas' disease

Thirteen communities from 7 Argentinian provinces were selected for the evaluation of serology as an indicator of transmission of Chagas disease. Of the communities appraised, 6 did not have a history of previous treatment with insecticides and 7 had received sporadic or continuous insecticide treatment. The inhabitants of 20% of the houses of each locality were studied by serology. The samples were obtained byfinger pricking and 50 fil of blood were mixed with 150μl of 50% glycerine solution in tissue culture media to be assayed by Indirect Hemagglutination and Indirect Immunofluorescence tests. In untreated areas, the prevalence of infection in infants 0-4 years old was 17.5%, reaching to over 22% for the 5-9 year old group, and to 33.3% in 10-14 year old individuals. The prevalence in treated and surveyed areas was 2.6% in 0-4 year old children, 5.4% in 5-9 year old and 6,2% in 10-14 year old youngsters. The differences between both areas were statistically significant (p < 0.005). This study favors serology as a valid indicator for the evaluation of transmission of Chagas disease in rural areas.

Reduction of spleen size in a child with Hyperreactive Malarious Splenomegaly (HMS) treated outside the Brazilian endemic area of malaria with only one course of quinine

We report the clinical picture, treatment and evolution of a child with hyperreactive malarious splenomegaly treated outside the endemic area of malaria. The patient presented gross splenomegaly, proceeded from an area where malaria is endemic, showed increased immunoglobulins levels, high antimalarial antibody titres and hepatic sinusoidal lymphocytosis. The child did not return to an area where malaria is endemic and showed a favorable response to only one course of quinine. The response of this patient to limited antimalarial therapy suggests the importance of reinfection with malaria in the development and maintenance of this syndrome.

Safety evaluation of SPF66 malaria vaccine in Brazil

The frequency and description of side effects secondaiy to the subcutaneous application of SPf66 malaria vaccine and placebo are reported for each dose of application in the participants of the vaccine efficacy trial in Brazil. Side effects evaluated two hours after each application were detected in 8.0%, 30.2% and 8.8%, for the Is', and 3"' dose, respectively, in the SPf66group, and in 7.0%, 8.5% and 2.9% in the placebo group. Local reactions such as mild inflammation, nodule and pain or erythema frequently accompanied by pruritus were the most common reactions detected in both groups (3-8%, 29.1% and 8.5% in the SPf66 group and 4.0%, 7.6% and 2.5% in the placebo group). Among vaccinees, local side effects after the 2nd dose were more frequent in females. Systemic side effects were expressed mainly through general symptoms referred by the participants and were most frequent after the 1st dose in both groups (4.3% in the SPf66 group and 3-0% in the placebo group). Muscle aches and fever were refewred by few participants. No severe adverse reactions were detected for either dose of application or group.

Pyruvate kinase and glucose-6-phosphate dehydrogenase deficies and their association with malaria - population genetics and proteomic studies

A malária é reconhecida como uma das principais forças selectivas a actuar na história recente no genoma humano. Inúmeros polimorfismos genéticos têm sido descritos como protectores contra a gravidade da malária, como o alelo HbS (designado de traço falciforme) e o alelo G6PD A- (associado à deficiência de G6PD). Mais recentemente, também a deficiência de PK foi associada com a protecção contra a malária. Evidências desta associação foram obtidas em estudos com modelos de roedor e estudos in vitro utilizando GV humanos deficientes em PK. Até à data, não foram obtidos dados em populações humanas que revelem esta associação: ainda não foi identificada uma variante de PK com uma prevalência elevada em regiões endémicas de malária e não foram identificadas marcas de selecção na região do gene que codifica para a PK (gene PKLR). Além disso, os mecanismos subjacentes à protecção contra a malária por deficiências enzimáticas dos GV não estão bem esclarecidos. Assim, os objectivos do presente estudo foram: investigar os polimorfismos genéticos humanos com associação com a malária em Cabo Verde; pesquisar marcas de selecção da malária na região do gene PKLR em populações Africanas; determinar a frequência da deficiência em PK e identificar uma eventual variante da enzima que possa estar sob selecção positiva em regiões endémicas de malária; avaliar o efeito das duas deficiências enzimáticas (PK e G6PD) na invasão e maturação do parasita em culturas in vitro de Plasmodium usando GV normais e deficientes; e analisar o perfil proteómico de GV infectados e não infectados, normais e com deficiência (em PK e G6PD), bem como de parasitas isolados de GV tanto deficientes como normais. Em Cabo Verde (área epidémica), não foram identificadas marcas de selecção pela malária, através da análise dos vários polimorfismos. No entanto, quando a análise foi realizada em dois países endémicos (Angola e Moçambique), foram detectadas várias marcas de selecção: a genotipagem de microssatélites (STRs) e polimorfismos de base única (SNPs) localizados na vizinhança do gene PKLR revelou uma diferenciação consideravelmente maior entre as populações Africana e Europeia (Portuguesa), do que a diferenciação determinada aquando da utilização de marcadores genéticos neutros. Além disso, uma região genómica de maior amplitude apresentou um Desequilíbrio de Ligação (LD) significativo no grupo de malária não grave (e não no grupo de malária grave), sugerindo que a malária poderá estar a exercer pressão selectiva sobre a região do genoma humano que envolve o gene PKLR. No estudo que incidiu na determinação da prevalência da deficiência de PK no continente Africano (realizado em Moçambique), esta revelou-se elevada - 4,1% - sendo o valor mais elevado descrito até ao momento a nível mundial para esta enzimopatia. Na pesquisa de mutações que pudessem estar na causa deste fenótipo (baixa actividade de PK), foi identificada uma mutação não sinónima 829G>A (277Glu>Lys), significativamente associada à baixa actividade enzimática. Esta mutação foi também identificada em Angola, São Tomé e Príncipe e Guiné Equatorial, onde a frequência de portadores heterozigóticos foi entre 2,6 e 6,7% (valores que se encontram entre os mais elevados descritos globalmente para mutações associadas à deficiência em PK). Não foi possível concluir acerca da associação entre a deficiência de PK e o grau de severidade da malária e da associação entre o alelo 829A e a mesma, devido ao baixo número de amostras. Os resultados dos ensaios de invasão/maturação do parasita sugeriram que, nos GV com deficiência de PK ou G6PD, a invasão (onde está envolvida a membrana do GV hospedeiro e o complexo apical do parasita) é mais relevante para a eventual protecção contra a malária do que a maturação. Os resultados da análise proteómica revelaram respostas diferentes por parte do parasita nas duas condições de crescimento (GV com deficiência de PK e GV com deficiência de G6PD). Esta resposta parece ser proporcional à gravidade da deficiência enzimática. Nos parasitas que cresceram em GV deficientes em G6PD (provenientes de um indivíduo assintomático), a principal alteração observada (relativamente às condições normais) foi o aumento do número de proteínas de choque térmico e chaperones, mostrando que os parasitas responderam às condições de stress oxidativo, aumentando a expressão de moléculas de protecção. Nos parasitas que cresceram em condições de deficit de PK (GV de indivíduo com crises hemolíticas regulares, dependente de transfusões sanguíneas), houve alteração da expressão de um maior número de proteínas (relativamente ao observado em condições normais), em que a maioria apresentou uma repressão da expressão. Os processos biológicos mais representados nesta resposta do parasita foram a digestão da hemoglobina e a troca de proteínas entre hospedeiro e parasita/remodelação da superfície do GV. Além disso, uma elevada percentagem destas proteínas com expressão alterada está relacionada com as fendas de Maurer, que desempenham um papel importante na patologia da infecção malárica. É colocada a hipótese de que a protecção contra a malária em GV deficientes em PK está relacionada com o processo de remodelação da membrana dos GV pelo parasita, o que pode condicionar a invasão por novos parasitas e a própria virulência da malária. Os resultados da análise do proteoma dos GV contribuirão para confirmar esta hipótese.

Report on ticks collected in the Southeast and Mid-West regions of Brazil: analyzing the potential transmission of tick-borne pathogens to man

Specimens of ticks were collected in 1993, 1996, 1997, and 1998, mostly from wild and domestic animals in the Southeast and Mid-West regions of Brazil. Nine species of Amblyommidae were identified: Anocentor nitens, Amblyomma cajennense, Amblyomma ovale, Amblyomma fulvum, Amblyomma striatum, Amblyomma rotundatum, Boophilus microplus, Boophilus annulatus, and Rhipicephalus sanguineus. The potential of these tick species as transmitters of pathogens to man was analyzed. A Flaviviridade Flavivirus was isolated from Amblyomma cajennense specimens collected from a sick capybara (Hydrochaeris hydrochaeris). Amblyomma cajennense is the main transmitter of Rickettsia rickettsii (=R. rickettsi), the causative agent of spotted fever in Brazil. Wild mammals, mainly capybaras and deer, infested by ticks and living in close contact with cattle, horses and dogs, offer the risk of transmission of wild zoonosis to these domestic animals and to man.

Molecular evidence of mother-to-child transmission of HTLV-IIc in the Kararao Village (Kayapo) in the Amazon Region of Brazil

Blood samples from native Indians in the Kararao village (Kayapo), were analysed using serological and molecular methods to characterize infection and analyse transmission of HTLV-II. Specific reactivity was observed in 3/26 individuals, of which two samples were from a mother and child. RFLP analysis of the pX and env regions confirmed HTLV-II infection. Nucleotide sequence of the 5' LTR segment and phylogenetic analysis showed a high similarity (98%) between the three samples and prototype HTLV-IIa (Mot), and confirmed the occurrence of the HTLV-IIc subtype. There was a high genetic similarity (99.9%) between the mother and child samples and the only difference was a deletion of two nucleotides (TC) in the mother sequence. Previous epidemiological studies among native Indians from Brazil have provided evidence of intrafamilial and vertical transmission of HTLV-IIc. The present study now provides molecular evidence of mother-to-child transmission of HTLV-IIc, a mechanism that is in large part responsible for the endemicity of HTLV in these relatively closed populations. Although the actual route of transmission is unknown, breast feeding would appear to be most likely.

Duffy blood group genotypes among malaria patients in Rondônia, Western Brazilian Amazon

We have compared Duffy blood group genotype distribution, as determined by polymerase chain reaction with allele-specific primers, in 68 Plasmodium vivax-infected patients and 59 non-vivax malaria controls from Rondônia, Brazil. Homozygosity for the allele Fy, which abolishes Duffy antigen expression on erythrocytes, was observed in 12% non-vivax controls but in no P. vivax patient. However, no significant association was found between Fy heterozygosity and protection against P. vivax. The Fy x allele, which has recently been associated with very weak erythrocyte expression of Duffy antigen, was not found in local P. vivax patients.

Outbreak of aggressions and transmission of rabies in human beings by vampire bats in northeastern Brazil

Outbreaks of attacks upon human beings by vampire bats seems to be a common phenomenon in several regions of Latin America, but the occurrence of rabies infection among humans bled by vampires, is relatively low. In the present study, two outbreaks of human rabies transmitted by common vampire bats (Desmodus rotundus) are described from Bahia State, Northeasthern Brazil, in 1991 and 1992. The first was recorded in Aporá where 308 people were bled by vampire bats and three of these die from this zoonosis. The 2nd outbreak occurred in Conde where only five people were bled by vampires, and two deaths by rabies were registered. Our data suggest that rabies transmitted by bats basically depends on the presence of virus in the vampire bat population and not on the number of humans bled by them.